We are employing DNA viruses as molecular probes to study genome expression in human cells. We are studying intensively the structure and function of adeno-associated virus (AAV) since this virus has only a small genome. AAV has also been developed as a eukaryotic expression vector. We are now analysing intensely the control of gene regulation in AAV vectors in order to maximize expression of foreign genes introduced into mammalian cells using this vector. We are studying also adenovirus which is a more complex genome. Adenovirus is the helper virus for AAV multiplication. This helper relationship is being analysed. Also both AAV and adenovirus recombine with cellular DNA. In the case of adenovirus this causes malignant transformation of the cell. AAV inhibits this transformation and also inhibits Ad12 oncogenesis in newborn animals. Thus AAV inhibits tumor induction. The mechanism of this inhibition of tumor induction is being studied at the molecular level in both cell culture and in animal experiments. We are also analysing gene expression and recombination in herpes simplex virus which is also a helper for AAV and has been linked to cervical carcinoma. We are also studying mutations in mouse 3T3 cells which render the cells resistant to malignant transformation by a single oncongene (ras) but allow malignant transformation by two oncogenes (ras, myc) acting in concert.